The overarching aim of this application is to develop an optimized combination package of HIV prevention services for men who have sex with men (MSM) in southern Africa, to develop preliminary data about the acceptability of the candidate package, and to develop a rational proposal for a subsequent efficacy trial of the prevention package. The rationale for this study is simple: virtually no work, in either research or programmatic areas, has focused on HIV preventive interventions for MSM in the Southern African region-despite emerging evidence that a severe epidemic of HIV is underway among these men. Communities of MSM are beginning to emerge in Southern Africa and they are doing so in the context of the world's most advanced and generalized epidemic of HIV. African MSM remain among the most hidden and stigmatized groups at risk in the HIV epidemic, and one for whom optimized prevention packages, fit to challenging local environments, are an urgent public health and research priority. Our group has conducted the first epidemiologic studies of MSM in Malawi, Namibia, Botswana, Lesotho and the first such studies among African and Colored MSM communities in peri-urban Cape Town. These studies have yielded expertise in how to safely conduct HIV research in these challenging environments, and have demonstrated the primacy of partnership with MSM and LGBT community organizations in the successful conduct of this critically needed research. We will use this expertise to develop our optimized HIV prevention package through four specific initiatives: conducting an umbrella review of literature on behavioral, biomedical, and structural interventions for MSM in Southern Africa; developing a mathematical model that accounts for sex with men, sex with women, circumcision status, insertivity ratios, ARV use, and the risk environment to estimate the impact on HIV transmission of implementation of a package of behavioral, biomedical, and community-level interventions; conducting pilot studies of acceptability and feasibility of the prevention package in Lusaka, Zambia and 2 predominately (black) African townships surrounding Cape Town, South Africa; and using preliminary information from the pilot study to design a larger, definitive study of the efficacy of the prevention package PUBLIC HEALTH RELEVANCE: Men who have sex with men in Africa are a largely hidden population at tremendous risk of HIV infection. This study proposes to use a process of review of existing knowledge and literature and mathematical modeling to develop a package of HIV prevention interventions for MSM in Africa, and to pilot test the acceptability of the package in Lusaka, Zambia and Cape Town, South Africa.